Amphetamine actions on pre- and postpubertal rat hippocampal dentate granule neurons

Clinical evidence suggests different actions of amphetamine (AMPH) in children and adults. Using intracellular recording techniques, the actions of AMPH at 10 and 40 microM were investigated in granule neurons of hippocampal slices from pre- and postpubertal rats. AMPH (10-40 microM) caused depolarization of most postpubertal neurons, often with increased spontaneous activity, whereas most prepubertal neurons were hyperpolarized. In both age groups, AMPH caused increased neuronal excitability by reducing spike threshold, attenuating the postspike train afterhyperpolarization, reducing spike frequency adaptation, and potentiating excitatory postsynaptic potentials. Changes in cell input resistance were variable and Ca2+ currents were unaffected. AMPH actions took 10-15 min to appear and became maximal 30-55 min after application. The effects were reversible at 10 microM, but at 40 microM, prolonged washout for up to 2 h did not completely reverse these actions. The beta-adrenergic blocker, propranolol, partially blocked AMPH actions. The dopamine (D2) blocker, haloperidol, did not block AMPH actions. Mature neurons were also tested with 2.5 microM AMPH showing similar but more reversible effects as the higher concentrations. Depleting catecholamines by reserpine partly attenuated the effects of 40 microM AMPH in mature neurons. Perfusion of neurons with 10 and 20 microM cocaine did not produce effects similar to those of AMPH. It is suggested that AMPH produces its effects on granule neurons only in part through the release of norepinephrine. The involvement of other neurotransmitters and/or neuromodulators released by AMPH, or direct postsynaptic actions of AMPH are also possible.